Th17 plasticity in human autoimmune arthritis is driven by the inflammatory environment

Nistala, Kiran; Adams, Stuart; Cambrook, Helen; Ursu, Simona; Olivito, Biagio; Jager, Wilco de; Evans, John M.; Cimaz, Rolando; Bajaj-Elliott, Mona; Wedderburn, Lucy R.

doi:10.1073/pnas.1003852107

Cited by 386 publications

(423 citation statements)

References 40 publications

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“…A similar conclusion was also obtained in humans; Nistala et al (36) showed Th17 to Th1 plasticity driven by the inflammatory environment in patients with autoimmune polyarthritis. Likewise, we have found an accumulation of CD4+ CD161+ T cells able to produce IFN-c (Th1), or both IFN-c and IL-17A (Th17/Th1), but not IL-17A alone (Th17), in the synovial fluid (SF) of children with oligoarticular juvenile idiopathic arthritis (JIA) (37).…”

Section: The Discovery Of Th17 Cells In Mice and Humanssupporting

confidence: 63%

Th17 cells: new players in asthma pathogenesis

Cosmi

Liotta

Maggi

et al. 2011

Allergy

288

198

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CD4+ T effector lymphocytes are distinguished in different subsets on the basis of their patterns of cytokine secretion. Th1 cells, thank to IFN-c production, are responsible for cell-mediated immunity against intracellular pathogens, Th2 cells, through the production of IL-4, provide some degree of protection against helminthes, and Th17 cells, via IL-17, promote neutrophils recruitment for the clearance of bacteria and fungi. However, beyond their protective role, these T-helper subsets can also be involved in the pathogenesis of several inflammatory diseases. Asthma is an inflammatory disease characterized by different clinical phenotypes. Allergic asthma is the result of an inflammatory process driven by allergen-specific Th2 lymphocytes, whereas Th17 cells are mainly involved in those forms of asthma, where neutrophils more than eosinophils, contribute to the inflammation. The identification in allergic asthma of Th17/Th2 cells, able to produce both IL-4 and IL-17, is in keeping with the observation that different clinical phenotypes can coexist in the same patient. In conclusion, a picture in which different T-cell subpopulations are active in different phase of bronchial asthma is emerging, and the wide spectrum of clinical phenotypes is probably the expression of different cellular characters playing a role in lung inflammation.

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Section: The Discovery Of Th17 Cells In Mice and Humanssupporting

confidence: 63%

Th17 cells: new players in asthma pathogenesis

Cosmi

Liotta

Maggi

et al. 2011

Allergy

288

198

View full text Add to dashboard Cite

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“…Another possibility is that Th1 cells may convert to Th17 cells or to an intermediate Th17/Th1 phenotype, which has been previously observed in patients with arthritis and in mice with experimental autoimmune encephalomyelitis (45,46). Regardless of the mechanisms leading to the shift from a primarily IFN␥ response early to a higher Th17/Th1 response later, we nevertheless observed that the frequencies and numbers of IL-17A-and IFN␥-producing CD4ϩ T cells were reduced in the inflamed paws of CXCR6 Ϫ/Ϫ mice compared to arthritic wild-type mice, providing one explanation for the reduced severity of arthritis in CXCR6 Ϫ/Ϫ mice.…”

Section: Discussionmentioning

confidence: 95%

Regulation of Cytokine Polarization and T Cell Recruitment to Inflamed Paws in Mouse Collagen‐Induced Arthritis by the Chemokine Receptor CXCR6

Slauenwhite

Gebremeskel

Doucette

et al. 2014

Arthritis & Rheumatology

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Objective. The chemokine receptor CXCR6 is highly expressed on lymphocytes isolated from the synovium of patients with rheumatoid arthritis, psoriatic arthritis, or juvenile idiopathic arthritis, suggesting that CXCR6 regulates immune cell activation or infiltration into arthritic joints. This study was undertaken to examine the role of CXCR6 in T cell activation and arthritis development.Methods. A collagen-induced arthritis model was used to examine arthritis development in wild-type and CXCR6 ؊/؊ mice. CXCR6 expression, lymphocyte accumulation, and intracellular cytokine production were examined by flow cytometry. Collagen-specific antibodies were measured in the serum. Collagen-specific recall responses were examined in vitro via proliferation and cytokine release assays. T cell homing to inflamed joints was examined using competitive adoptive transfer of dye-labeled lymphocytes from wild-type and CXCR6 ؊/؊ mice.Results. The numbers of CXCR6؉ T cells were increased in the paws and draining lymph nodes of arthritic mice. The incidence of arthritis, disease severity, extent of T cell accumulation, and levels of collagenspecific IgG2a antibodies were significantly reduced in CXCR6 ؊/؊ mice compared to wild-type mice. Conclusion. These experiments demonstrate that CXCR6 plays important roles in the pathogenesis of arthritis through its effects on both T cell cytokine polarization and homing of T cells to inflamed joints.

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“…Furthermore, some studies, especially in autoimmune diseases, proposed that the Th17 phenotype is unstable and that Th17 cells may convert to Th1 cells. 26 We can suggest that in a context of gastrointestinal aGVHD, some Th17 cells infiltrate early the intestinal mucosa and then can differentiate into Th1 cells making their detection more difficult if intestinal biopsies are performed too late after the onset of aGVHD. Recently, Esplugues et al 27 proposed a general mechanism for controlling immunopathogenic Th17 response by acquisition of an immune-suppressive phenotype or elimination into the intestinal lumen.…”

Section: Th17 and Plasmacytoid Dendritic Cells In Agvhd C Bossard Et Almentioning

confidence: 99%

Plasmacytoid dendritic cells and Th17 immune response contribution in gastrointestinal acute graft-versus-host disease

et al. 2012

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The contribution of Th17 cells in acute graft-versus-host disease (aGVHD) has been demonstrated in aGVHD mouse models. However, their contribution in human gastrointestinal aGVHD remains unclear. We evaluated Th17 cells in a cohort of 23 patients at diagnosis of aGVHD. In this study, we have shown that the absolute number of Th17 cells using the CCR6 and CD161 markers were significantly higher in the intestinal mucosa of patients with aGVHD compared with intestinal mucosa of patients without aGVHD. Moreover, in keeping with the increase of CCR6 þ and CD161 þ T cells, RORgt the key transcription factor that orchestrates the differentiation of Th17 cells, was significantly increased in the intestinal mucosa of patients with aGVHD compared with intestinal mucosa of patients without aGVHD (P ¼ 0.01). Since plasmacytoid dendritic cells (PDCs) have been reported to drive the differentiation of the Th17 subset, we quantified PDCs in these patients. PDC CD123 þ cells were increased in the intestinal mucosa of patients with aGVHD. Furthermore, the number of CD123 þ PDCs paralleled the histological grade of aGVHD, providing evidence for a role of Th17-mediated responses and a potential new pathophysiological link between PDCs and Th17 in human aGVHD.

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Th17 plasticity in human autoimmune arthritis is driven by the inflammatory environment

Cited by 386 publications

References 40 publications

Th17 cells: new players in asthma pathogenesis

Th17 cells: new players in asthma pathogenesis

Regulation of Cytokine Polarization and T Cell Recruitment to Inflamed Paws in Mouse Collagen‐Induced Arthritis by the Chemokine Receptor CXCR6

Plasmacytoid dendritic cells and Th17 immune response contribution in gastrointestinal acute graft-versus-host disease

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